Heat-stable plasma constituent responsible for caspase activation in Hashimoto's thyroiditis
Article first published online: 6 DEC 2002
© 2000 British Journal of Surgery Society Ltd
British Journal of Surgery
Volume 87, Issue 9, page 1258, 1 September 2000
How to Cite
Palazzo, F. F., Hammond, L. J., Murphy, B. J., Goode, A. W. and Mirakian, R. (2000), Heat-stable plasma constituent responsible for caspase activation in Hashimoto's thyroiditis. Br J Surg, 87: 1258. doi: 10.1046/j.1365-2168.2000.01601-6.x
- Issue published online: 6 DEC 2002
- Article first published online: 6 DEC 2002
- Cited By
Autoimmune thyroid disease is characterized by a spectrum of thyroid activity, with Graves disease (GD) and Hashimoto's thyroiditis (HT) at the extremes of over and under activity respectively. Hypothyroidism in HT is caused by apoptotic thyrocyte death, which is achieved via a cascade of cysteine protease (caspase) activity. It is still unclear whether thyrocyte death is the result of caspase activation secondary to extrinsic Fas/FasL interaction with the activation of procaspase 8 and/or of cytochrome C release from thyrocyte mitochondria consequent to impaired expression of the Bcl2/Bcl-X thyrocyte survival genes. This study was designed to clarify whether plasma constituents have a role in thyrocyte apoptosis and whether differential apoptotic kinetics can be observed in thyroid diseases.
Cultured thyrocytes from fresh surgical specimens were incubated with 5 and 20 per cent plasma from patients with multinodular goitre (MNG), GD and HT for between 5 and 180 min. Procaspase 8, caspase 3 and cytochrome C activities were monitored using Western blotting on thyroid lysates. Procaspase 8 was also studied microscopically using light microscopy and immunofluoroscopy. To ascertain the role of complement activity in the induction of apoptosis, thyrocytes from MNG, GD and HT thyroids were also exposed to heat-treated plasma (56°C for 45 min) for varying time intervals before caspase 8 estimation.
Western blot and immunofluoroscopy confirmed that human plasma induces procaspase 8 in thyrocytes; Western blots also showed activation of cytochrome C and caspase 3 in these cells. At 30 min and up to 90 min thyrocyte procaspase 8 expression and the expression of breakdown products of this protein appeared to be more marked in the thyrocytes treated with HT plasma than MNG and GD plasma. Procaspase 8 expression was not altered by the heat of plasma. Thyrocytes exposed to plasma of patients with autoimmune and non-autoimmune conditions showed similar bands for caspase 3 and cytochrome C. The cytochrome C signal was stronger in the cells exposed to HT plasma at 30 min.
A heat-stable constituent of human plasma induces programmed cell death in thyrocytes. Plasma from patients with HT appears to induce a greater death stimulus than that from patients with other thyroid conditions. Fas/FasL interaction appears to be involved in apoptotic thyrocyte death. The role of mitochondrial cytochrome C in the induction of cell death is unclear. © 2000 British Journal of Surgery Society Ltd